Faculty Collaboration Database

Inhibition of nitric oxide synthase attenuates NNMU-induced alveolar injury in vivo. Am J Physiol 1997 Dec;273(6):L1167-73

Date

01/22/1998

Pubmed ID

9435571

DOI

10.1152/ajplung.1997.273.6.L1167

Scopus ID

2-s2.0-0031408789 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

The purpose of this study was to determine if the acute alveolar injury induced by subcutaneous injections of N-nitroso-N-methylurethane (NNMU) in rats is mediated by nitric oxide (NO.). We show that intraperitoneal injections of the NO. synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine significantly attenuate the NNMU-induced alveolar injury as assessed by 1) normalization of the alveolar-arterial O2 difference, 2) attenuation of the lowered phospholipid-to-protein ratio in the crude surfactant pellet (CSP), 3) attenuation of the elevated minimal surface tension of the CSP, and 4) attenuation of polymorphonuclear neutrophilic infiltration into the alveolar space. Injections of N omega-nitro-D-arginine methyl ester, the inactive stereoisoform of L-NAME, did not affect the acute lung injury. Western blot analysis of whole lung homogenates demonstrate an elevated expression of transcriptionally inducible, Ca(2+)-independent NOS (iNOS) in NNMU-injected rats compared with control saline-injected rats. NOS inhibitors did not affect NNMU-induced iNOS expression. These investigations demonstrate that the inhibition of NOS attenuates NNMU-induced acute lung injury, suggesting a role for NO. in the progression of acute respiratory distress syndrome.

Author List

Cruz WS, Moxley MA, Corbett JA, Longmore WJ

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bronchoalveolar Lavage Fluid
Guanidines
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrosomethylurethane
Oxygen
Pulmonary Alveoli
Pulmonary Circulation
Pulmonary Surfactants
Rats
Rats, Sprague-Dawley